Local data support continuation of RASIs in patients with T2D and advanced CKD

Discontinuation of renin-angiotensin system inhibitors (RASIs) is associated with higher risks of cardiorenal complications and neutral risk of all-cause mortality in patients with type 2 diabetes (T2D) and advanced chronic kidney disease (CKD), according to researchers from the Chinese University of Hong Kong (CUHK).

“While use of RASIs in early CKD is widely accepted, the risk-benefit [profile] of RASI continuation in advanced CKD has been a subject of debate,” wrote the researchers. “In real-world practice, 15–30 percent of patients with advanced CKD had discontinued RASIs due to concerns of hyperkalaemia or acute decline in kidney function.”

The researchers have therefore conducted a prospective, population-based cohort study in Chinese patients with T2D and advanced CKD treated with RASIs (n=10,400; mean age, 73.1 years; mean diabetes duration, 14.0 years), using 2002–2018 data from the Hong Kong Diabetes Surveillance Database. In the study, 1,766 patients discontinued RASIs, while 8,634 patients persisted with RASI treatment. [EClinicalMedicine 2022;55:101751]

During a median follow-up of 3.6 years, 13.5 percent, 12.9 percent, and 27.6 percent of patients had incident major adverse cardiovascular event (MACE), heart failure (HF), and end-stage kidney disease (ESKD), respectively, and 35.8 percent of patients died.

Compared with RASI continuation, discontinuation of RASIs was associated with significantly increased risk of MACE (hazard ratio [HR], 1.27; 95 percent confidence interval [CI], 1.08–1.49; p=0.003), HF (HR, 1.85; 95 percent CI, 1.53–2.25; p<0.001), and ESKD (HR, 1.30; 95 percent CI, 1.17–1.43; p<0.001), but no significant difference in all-cause mortality (HR, 0.93; 95 percent CI, 0.86–1.01; p=0.097) was found. Similarly, both permanent discontinuation and stop-restart discontinuation of RASIs were associated with worse cardiorenal outcomes vs continued RASI use. “RASIs not only protect the kidneys, but also reduce other cardiovascular outcomes such as stroke and heart attack,” highlighted Professor Juliana Chan of the Department of Medicine and Therapeutics, CUHK.

In contrast with findings of some previous studies, subgroup analyses showed a similar risk of first event of hyperkalaemia over a 5-year period in patients with T2D and new-onset estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² who were continued RASI users or discontinued RASI users (HR, 0.95; 95 percent CI, 0.84–1.08; p=0.42). “The risk of hyperkalaemia was only apparent at a higher dose of RASI,” added the researchers.

“RASIs were often discontinued for various reasons in patients with CKD. However, many patients with CKD can safely continue and benefit from RASIs by avoiding nephrotoxic drugs, adjusting dietary potassium intake and measuring kidney function regularly,” suggested Dr Elaine Chow of the Department of Medicine and Therapeutics, CUHK. “[Additionally], the dose of RASI can be adjusted based on kidney function and potassium levels, with discontinuation only as a last resort.”

In summary, use of RASIs showed no clear link to risk of hyperkalaemia in patients with T2D and advanced CKD. These local real-world data support continuation of RASIs in patients with T2D and advanced CKD for cardiorenal protection.